The focus of our research centers around the interferon defense system - induction, regulation, site(s) and mechanism(s) of action. Interferons are glycoproteins which are synthesized in a variety of cells of vertebrates upon viral infection or some other stimuli. They are excreted, bound to other cells and render these cells, by inducing an antiviral protein, inefficient in supporting the growth of a broad range of viruses. Experiments are proposed which will seek to determine whether the normal mode of synthesis and processing of viral mRNA is altered in cells treated with interferon. Particular attention will be paid to initial RNA transcripts from infecting viral particles in the absence of RNA transcripts contributed by progeny virions (amplification). The general scheme by which viral mRNA metabolism will be investigated includes labeling infected cells with 3H-uridine in the presence of actinomycin D to suppress host RNA synthesis followed by sedimentation velocity analysis in sucrose gradients and molecular hybridization of viral RNA transcripts with viral genome. Initial RNA transcripts from infecting viral particles will be investigated by making use of particular characteristics of the following viral systems: Reovirus type 3, Avian Reovirus S1133, and Vesicular Stomatitis Virus.